A rare opportunity is presented at Children's Hospital to study a diverse assortment of heritable diseases that affect the development and normal function of the skeleton. These include osteogenesis imperfecta, the many skeletal dysplasias, the various sub-types of Ehlers-Danlos syndrome, Marfan's syndrome, idiopathic scoliosis and many other less well known or previously undescribed heritable conditions. In a closely coordinated, parallel approach it is planned to seek abnormalities in the molecular structure of collagen and other structural macromolecules by biochemical analysis and in the ultrastructure of the cells and extracellular matrix of the affected connective tissues by electron microscopy. Collagen will be analyzed for solubility, molecular types, molecular weight of component alpha-chains, full range of crosslinking amino acids including newly identified non-reducible forms, content of hydroxylsine and hydroxylysine glycosides, and further compositional and biosynthetic properties of the individual alpha-chains dependent on the clinical condition and results of preliminary analyses. For abnormal cartilages, aspects of proteoglycan and glycoprotein compositions will be examined. The diameter, weave and appearance of the collagen fibrils will be determined by electron microscopy, and also the distribution of proteoglycans in cartilage and other tissues by staining with ruthenium red. The ultrastructure of cells in the affected tissues will be studied, looking particularly for abnormalities in organelles that handle the export and resorption of matrix materials.